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GTR Home > Conditions/Phenotypes > Esomeprazole response

Esomeprazole response

Synonyms
Nexium response

Summary

Esomeprazole (brand name Nexium) is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease (GERD) and to reduce the risk of gastric ulcers associated with nonsteroidal anti-inflammatory drug NSAID use. Esomeprazole is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection. Esomeprazole reduces the acidity (raises the pH) in the stomach by inhibiting the secretion of gastric acid. The level of esomeprazole an individual is exposed to is influenced by several factors, such as the dose used and how quickly the drug is metabolized and inactivated. Esomeprazole is primarily metabolized by the CYP2C19 enzyme. Individuals with increased CYP2C19 enzyme activity (“CYP2C19 ultrarapid metabolizers”) may have an insufficient response to standard doses of esomeprazole, because the drug is inactivated at a faster rate. In contrast, individuals who have reduced or absent CYP2C19 enzyme activity (i.e., CYP2C19 intermediate and poor metabolizers) have a greater exposure to esomeprazole. The 2018 FDA-approved drug label for esomeprazole states that 3% of Caucasians, and 15–20% of Asians are CYP2C19 poor metabolizers, and that poor metabolizers have approximately twice the level of exposure to esomeprazole, compared with CYP2C19 normal metabolizers. However, the drug label does not include dosing recommendations for CYP2C19 poor metabolizers. Esomeprazole recommendations have been published by the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), which indicates that no change in dosing is recommended for CYP2C19 poor, intermediate, or ultrarapid metabolizers. The DPWG states that although genetic variation in CYP2C19 influences the plasma concentration of esomeprazole, there is insufficient evidence to support an effect on treatment outcomes or side effects. [from Medical Genetics Summaries]

Available tests

13 tests are in the database for this condition.

Check Related conditions for additional relevant tests.

Clinical tests (13 available)

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: CPCJ, CYP2C, CYPIIC17, CYPIIC19, P450C2C, P450IIC19, CYP2C19
    Summary: cytochrome P450 family 2 subfamily C member 19

  • Also known as: CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4, HLP, NF-25, P450C3, P450PCN1, VDDR3, CYP3A4
    Summary: cytochrome P450 family 3 subfamily A member 4

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted1information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2018 Statement from the US Food and Drug Administration (FDA)

Metabolism

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP3A4, which forms the sulphone metabolite. CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Normal Metabolizers) is approximately 2.

[...]

Interaction with Clopidogrel

Avoid concomitant use of esomeprazole magnesium with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole reduces the pharmacological activity of clopidogrel. When using esomeprazole magnesium consider alternative anti-platelet therapy.

Please review the complete therapeutic recommendations located here: (1).

2018 Summary of recommendations from the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)

CYP2C19 Poor Metabolizer (PM)

No action is needed for this gene-drug interaction.

Although the genetic variation leads to a higher plasma concentration of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.

CYP2C19 Intermediate Metabolizer (IM)

No action is needed for this gene-drug interaction.

Although the genetic variation leads to a higher plasma concentration of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.

CYP2C19 Ultrarapid Metabolizer (UM)

No action is required for this gene-drug interaction.

Although the genetic variation may lead to faster inactivation of esomeprazole, there is insufficient evidence to support an effect on the therapeutic effectiveness and side effects.

Background information

For more information about the PM, IM, and UM phenotypes: see the general background information about CYP2C19 on the KNMP Knowledge Bank or on www.knmp.nl (search for CYP2C19). Access requires KNMP membership.

Please review the complete therapeutic recommendations that are located here: (2).

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance with nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.

Reviews

Clinical resources

Practice guidelines

  • DPWG, 2023
    Royal Dutch Pharmacists Association (KNMP). Dutch Pharmacogenetics Working Group (DPWG). Pharmacogenetic Recommendation.

Molecular resources

Consumer resources

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